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Background and study aims The optimal intragastric pressure (IP) for strong gastric wall extension is unclear. We aimed to develop an accurate method to measure IP using endoscopy and determine the pressure required for strong gastric wall extension. Methods An in vitro experiment using an endoscope with a rubber attached at its tip was conducted. The process of inserting the pressure measurement probe into the forceps channel was skipped, and the tube of the pressure measurement device was directly connected to the forceps channel. In vivo, the pressure in 51 consecutive patients at the time of strong gastric wall extension was measured. Strong extension of the gastric wall was defined as when the folds in the greater curvature were flattened as a result of sufficient extension of the gastric wall by insufflated air during upper gastrointestinal endoscopy. The IP at that time was measured. Results In vitro, 20 mL of tap water was injected once into the forceps channel and then aspirated for 10 seconds. Pressure measurement after irrigation of the forceps channel as well as the measurement by inserting the probe procedure were accurately performed. In vivo, among the 51 included patients, the mean IP (range) was 14.7 mmHg (10–23). Strong extension of the gastric wall was obtained in 96.1 % of patients when the IP was 20 mmHg. Conclusions We developed an accurate method to measure IP using upper gastrointestinal endoscopy. Strong extension of the gastric wall was obtained in almost all patients when the IP was 20 mmHg.

Background/Aims The objective of this study was to elucidate the histological structure of the absent microsurface patterns (MSPs) that were visualized by magnifying endoscopy with narrow-band imaging (M-NBI). Methods The study included consecutive gastric epithelial neoplasias for which M-NBI findings and histological findings could be compared on a one-to-one basis. The lesions were classified as absent MSPs and present MSPs based on the findings obtained using M-NBI. Of the histopathological findings for each lesion that corresponded to M-NBI findings, crypt opening densities, crypt lengths, crypt opening diameters, intercrypt distances, and crypt angles were measured and compared. Results Thirty-six lesions were included in the analysis; of these, 17 lesions exhibited absent MSP and 19 lesions exhibited present MSP. Comparing the histological measurements for absent MSPs vs. present MSPs, median crypt opening density was 0.9 crypt openings/mm vs. 4.8 crypt openings/mm (p

The Japan Gastroenterological Endoscopy Society developed the Guideline for Endoscopic Diagnosis of Early Gastric Cancer based on scientific methods. Endoscopy for the diagnosis of early gastric cancer has been acknowledged as a useful and highly precise examination, and its use has become increasingly more common in recent years. However, the level of evidence in this field is low, and it is often necessary to determine recommendations based on expert consensus only. This clinical practice guideline consists of the following sections to provide the current guideline: [I] Risk stratification of gastric cancer before endoscopic examination, [II] Detection of early gastric cancer, [III] Qualitative diagnosis of early gastric cancer, [IV] Diagnosis to choose the therapeutic strategy for gastric cancer, [V] Risk stratification after endoscopic examination, and [VI] Surveillance of early gastric cancer.

With the improvement in endoscopic equipment functions, narrow-band imaging (NBI) for endoscopic observation of the stomach, which is an organ with a large lumen, is now feasible. Studies evaluating the NBI utility without magnifying endoscopy to diagnose the invasion extent for the demarcation line identification in early gastric cancer have not been reported. This study aimed to investigate the demarcation line diagnostic performance of NBI in early gastric cancer compared to that of white-light imaging (WLI) using prospectively collected consecutive specimens from early gastric cancer patients.Thirty consecutive lesions were collected from patients who underwent endoscopic submucosal dissection for early gastric cancer. Next, 30 NBI and 30 WLI images, each with the same degree of gastric wall extension, angle, and layout for one lesion, were selected, and a total of 60 images were prepared for testing. The early gastric cancer invasion ranges in the endoscopic images was plotted using the web-developed software, and 264 independent endoscopists, unaware of the diagnosis, performed the web tests, with the concordance rates between the ranges of responses. After estimating the actual early gastric cancer invasion ranges, the NBI and WLI results were compared.The concordance rates for NBI and WLI images were 43.1% (95% confidence interval [CI] 42.5-43.7%) and 37.2% (95% CI 36.6-37.7%), respectively, showing that the concordance rate for NBI was significantly higher than that for WLI.This study suggested that NBI was more useful for identifying demarcation lines than WLI.

Subepithelial microvascular pattern cannot be visualized on the surface of adenoma and carcinoma by magnifying endoscopy due to a white opaque substance (WOS), which consists of minute lipid droplets accumulated in the neoplastic epithelium.We aimed to investigate whether the WOS is visualized in the duodenum after exogenous fat loading (FL) administration in an open-label, randomized, controlled study.The patients scheduled to undergo endoscopic therapy for gastric epithelial neoplasms were enrolled in the study. They were randomly assigned to the FL or non-FL group. An initial (before FL administration) and follow-up (after two to three weeks) endoscopic examinations were conducted to observe the duodenal mucosa using magnifying narrow-band imaging. Each patient in the FL group consumed 250 ml of Ensure H® four hours before the follow-up examination. Two experienced endoscopists determined the grade of the WOS. FL test results were judged positive for patients who showed a higher grade at the follow-up examination than at the initial examination. The rate of positive test results was compared between the two groups.Twenty patients (10 in the FL and 10 in the non-FL groups) were included. FL test results were positive for all 10 patients in the FL group, while they were negative for all 10 patients in the non-FL group (P 0.001 by Fisher's exact test).Lipids loaded onto normal duodenal epithelium were absorbed, and the absorbed lipid droplets appeared as WOS on magnifying narrow-band imaging.

Background and study aims We developed an e-learning program for endoscopic diagnosis of invasion depth of early gastric cancer (EGC) using a simple diagnostic criterion called non-extension sign, and the contribution of self-study quizzes to improvement of diagnostic accuracy was evaluated. Methods We conducted a prospective randomized controlled study that recruited endoscopists throughout Japan. After completing a pretest, the participants watched video lectures and undertook post-test 1. The participants were then randomly allocated to either the self-study or non-self-study group, and participants in the first group completed the self-study program that comprised 100-case quizzes. Finally, participants in both groups undertook post-test 2. The primary endpoint was the difference in post-test 2 scores between the groups. The perfect score for the tests was set as 100 points. Results A total of 423 endoscopists completed the pretest and were enrolled. Post-test 1 was completed by 415 endoscopists and 208 were allocated to the self-study group and 207 to the non-self-study group. Two hundred and four in the self-study group and 205 in the non-self-study group were included in the analysis. Video lectures improved the mean score of post-test 1 from 72 to 77 points. Participants who completed the self-study quizzes showed significantly better post-test 2 scores compared with the non-self-study group (80 vs. 76 points, respectively, P Conclusions Our e-learning program showed that self-study quizzes consolidated knowledge of the non-extension sign and improved diagnostic ability of endoscopists for invasion depth of EGC.

Background: Determining the depth of invasion is important when considering therapeutic strategies for early gastric cancer (EGC). We determined the effects of learning the non-extension sign, that is, an index of T1b2 in EGC, on identifying its depth of invasion. Methods: Endoscopic images of 40 EGC cases (20 showing positive non-extension sign on endoscopy as T1b2 and 20 showing negative non-extension sign on endoscopy as T1a-T1b1) were randomly displayed on PowerPoint. Participants read endoscopy findings (pretest) and attended a 60-min lecture on how to read the non-extension sign. Then, they read the same images using the non-extension sign as the marker (posttest). The primary endpoint was a change in accuracy rate for determining the depth of invasion before and after attending the lecture, for nonexperts (< 80%). Results: Among 35 endoscopists, 12 were nonexperts; their test results were used for analyses. Accuracy rates for pretest and posttest among nonexperts were 75.2 and 82.5%, respectively, showing a significant increase in the accuracy rate after learning to read the non-extension sign (p = 0.003). Conclusion: Nonexperts’ diagnostic ability to determine the depth of invasion of EGC improved by learning to read the non-extension sign. Thus, the non-extension sign is considered a simple and useful diagnostic marker.

Distinguishing undifferentiated-type from differentiated-type early gastric cancers (EGC) is crucial for determining the indication of endoscopic resection. We aimed to investigate the diagnostic performance of white-light endoscopy (WLE) and magnifying narrow-band imaging (M-NBI) for the histological type of EGC.In this multicenter prospective study, patients with histologically proven cT1 EGC, macroscopically depressed or flat type, size ≥5 mm, and without erosion/ulcer, were recruited. The diagnostic criterion of WLE for undifferentiated-type EGC was pale color. The M-NBI algorithm was created based on microsurface and microvascular patterns, and lesions with absent microsurface pattern and opened-loop microvascular patterns were diagnosed as undifferentiated-type. The center of the lesion was defined as the evaluation point and was initially evaluated by WLE, then by M-NBI, and a biopsy specimen was taken as a reference standard. The primary and key secondary endpoints were overall diagnostic accuracy and specificity, respectively.In total, 167 lesions (122 differentiated-type and 45 undifferentiated-type EGCs) in 167 patients were analyzed. The overall accuracy, sensitivity, specificity, and positive likelihood ratio of WLE for undifferentiated-type cancer were 80%, 69%, 84%, and 4.4, respectively, and those of M-NBI were 82%, 53%, 93%, and 7.2, respectively. There was no significant difference in overall accuracy (The use of M-NBI did not improve the accuracy of WLE for the diagnosis of depressed/flat undifferentiated-type EGCs but improved the specificity. It may reduce surgical overtreatment by preventing misdiagnosis of differentiated-type EGC as undifferentiated-type.

ObjectiveDistinguishing undifferentiated-type (diffuse-type) from differentiated-type (intestinal-type) cancer is crucial for determining the indication of endoscopic resection for gastric cancer. This study aimed to evaluate on-site diagnostic performance of conventional white-light endoscopy (WLE) and magnifying narrow-band imaging (M-NBI) in determining the subtype of gastric cancer.DesignWe conducted a multicenter prospective single-arm trial. Patients who planned to undergo treatment for histologically proven cT1 gastric cancer were recruited from six tertiary care institutions. The primary and key secondary endpoints were diagnostic accuracy and specificity, respectively. The diagnostic algorithm of WLE was based on lesion color. The M-NBI algorithm was based on the microsurface and microvascular patterns.ResultsA total of 208 patients were enrolled. After protocol endoscopy, 167 gastric cancers were included in the analysis. The accuracy, sensitivity, specificity, and positive likelihood ratio of WLE for undifferentiated-type cancer were 80% (95% CI 73%–86%), 69% (53%–82%), 84% (77%–90%), and 4.4 (2.8–7.0), respectively. Those of M-NBI were 82% (75%–88%), 53% (38%–68%), 93% (87%–97%), and 7.2 (3.6–14.4), respectively. There was no significant difference in accuracy between WLE and M-NBI (p=0.755), but specificity was significantly higher with M-NBI than with WLE (p=0.041). Those of M-NBI combined with WLE were 81% (74%–87%), 38% (24%–54%), 97% (92%–99%), and 11.5 (4.1–32.4), respectively.ConclusionM-NBI is more specific than WLE in distinguishing undifferentiated-type from differentiated-type gastric cancer and M-NBI combined with WLE is highly reliable (positive likelihood ratio >10).Trial registration numberUMIN000032151.Significance of this studyWhat is already known on this subject?➢Distinguishing gastric cancer from non-cancer using endoscopy has already been validated.➢However, distinguishing undifferentiated-type (diffuse-type) from differentiated-type (intestinal-type) cancer is also crucial for determining the indication of endoscopic resection for gastric cancer.➢Several studies have proposed the characteristic findings of the subtype of gastric cancer in white-light endoscopy and magnifying narrow-band imaging.What are the new findings?➢Magnifying narrow-band imaging was more specific than white-light endoscopy in distinguishing undifferentiated-type gastric cancer from differentiated-type gastric cancer.➢The positive likelihood ratio of these combined modalities for undifferentiated-type cancer was highly reliable (>10).➢The present study verified the diagnostic characteristics and potential for clinical use of these two modalities.How might it impact on clinical practice in the foreseeable future?➢This study’s results, which included the positive likelihood ratio, suggest that optical biopsy may be introduced into the decision making of endoscopic treatment for gastric cancer.➢If optical biopsy based on these results is applied, the risk of surgical overtreatment is estimated to be low, leading to practical decision making.

Background and study aims Magnifying endoscopy with narrow-band imaging (M-NBI) is reported to be useful in diagnosing invasion depth of superficial esophageal squamous cell carcinoma (SCC), but accurate diagnosis of deep submucosal invasion (SM2) has remained difficult. However, we discovered that irregularly branched microvessels observed with M-NBI are detected in SM2 cancers with high prevalence. Thus, this retrospective study aimed to investigate the diagnostic performance of irregularly branched microvessels as visualized by M-NBI for predicting SM2 cancers. Patients and methods Patients with superficial esophageal SCC lesions that were endoscopically or surgically resected at our hospital between September 2005 and December 2014 were included. Endoscopic findings by M-NBI of these lesions were presented to an experienced endoscopist who was unaware of the histopathological diagnosis and who then judged whether irregularly branched microvessels were present. Using the invasion depth according to postoperative histopathological diagnosis as the gold standard, we determined the diagnostic performance of the presence of irregularly branched microvessels as an indicator for SM2 cancers. Results A total of 302 superficial esophageal SCC lesions (228 patients) were included in the analysis. When irregularly branched microvessels were used as an indicator of SM2 cancers, the diagnostic accuracy was 94.0 % (95 % confidence interval [CI]: 91.1–96.1 %), sensitivity was 79.4 % (95 % CI: 66.6–88.4 %), specificity was 95.9 % (95 % CI: 94.3–97.0 %), positive predictive value was 71.1 % (95 % CI: 59.6–79.1 %), and negative predictive value was 97.3 % (95% CI: 95.7–98.5 %). Conclusions Irregularly branched microvessels may be a reliable M-NBI indicator for the diagnosis of cancers with deep submucosal invasion.

Background Accurate delineation of tumor margins is necessary for curative resection of early gastric cancer (EGC). The objective of this multicenter, randomized, controlled study was to compare the accuracy with which magnifying narrow-band imaging (M-NBI) and indigo carmine chromoendoscopy delineate EGC margins. Methods Patients with EGC ≥ 10 mm undergoing endoscopic or surgical resection were enrolled. The oral-side margins of the lesions were first evaluated with conventional white-light endoscopy in both groups and then delineated by either chromoendoscopy or M-NBI. Biopsies were taken from noncancerous and cancerous mucosa, each at 5 mm from the margin. Accurate delineation was judged to have been achieved when the histological findings in all biopsy samples were consistent with endoscopic diagnoses. The primary end point was the difference in rate of accurate delineation between the two techniques. Results Data on 343 patients were analyzed. The accurate delineation rate (95 % confidence interval) was 85.7 % (80.4 – 91.0) in the chromoendoscopy group (n = 168), and 88.0 % (83.2 – 92.8) in the M-NBI group (n = 175; P = 0.63). Lower third tumor location (odds ratio [OR] 2.9; P = 0.01), nonflat macroscopic type (OR 4.4; P Conclusions M-NBI does not offer superior delineation of EGC margins compared with chromoendoscopy; the two methods appear to be clinically equivalent.

The ability to differentiate between mucosal (M) or microinvasive submucosal (SM1: depth of less than 500 µm) and invasive submucosal (SM2: depth of 500 µm or more) cancer is paramount when choosing the method of treatment for early gastric cancer (EGC). The "non-extension sign" relates to a localized increase in thickness and rigidity due to massive submucosal invasion by a cancer. The present study sought to assess the ability of conventional endoscopy (CE) to correctly identify SM2 cancer using only the non-extension sign.This is a retrospective study based on a prospectively collected database. EGCs had been diagnosed according to invasion depth as M-SM1 or SM2. In terms of the endoscopic diagnostic criterion, lesions positive for the non-extension sign were classified as SM2 cancers, while those negative for the non-extension sign were classified as M-SM1 cancers. Histopathological findings were used as the gold standard.We examined a total of 863 lesions from 704 patients, comprising 104 true-positive, 733 true-negative, 9 false-positive, and 17 false-negative lesions. This yielded a sensitivity of 92.0 % (95 % confidence interval (CI), 87.0-97.0 %), a specificity of 97.7 % (95 % CI, 96.7-98.8 %), a positive predictive value of 85.9 % (95 % CI, 79.7-92.1 %), a negative predictive value of 98.8 % (95 % CI, 98.0-99.6 %), and a diagnostic accuracy of 96.9 % (95 % CI, 95.8-98.1 %).The non-extension sign may be useful for accurately determining the suitability of minimally invasive endoscopic treatment. Nevertheless, considering the limitations of retrospective analysis, a further prospective study is warranted to confirm the diagnostic reliability of the non-extension sign.

Background and aim White opaque substance (WOS) is a novel endoscopic finding in gastric neoplasms, indicating the intracellular accumulation of lipid droplets (LDs). However, gastric lipid metabolism has not been extensively investigated, even in normal mucosa. We investigated the expression profiles of lipid-metabolism-associated genes in gastric neoplasms. Methods Thirty-four patients with early gastric cancer or adenoma were enrolled in this study. Paired biopsy samples from tumor and adjacent non-tumor areas were obtained and analyzed by real-time polymerase chain reaction. Endoscopically resected specimens were evaluated histopathologically. Results Genes associated with β-oxidation (peroxisome proliferator-activated receptor α, carnitine palmitoyltransferase 1A, and hydroxyacyl-CoA dehydrogenase), lipoprotein excretion (apolipoprotein B, microsomal triglyceride transfer protein, and acyl-CoA:cholesterol acyltransferase 2), fatty acid transport (fatty acid-binding protein), construction of triglycerides in the endoplasmic reticulum (acyl-CoA:diacylglycerol acyltransferase 1), and LD degradation/lipolysis (comparative gene identification-58, adipose triglyceride lipase) were significantly downregulated in neoplasms compared with non-tumor areas. Pyruvate dehydrogenase lipoamide kinase isozyme 4 (negative regulator of glycolysis) and adipophilin (LD surface component) were also repressed. Conversely, expression levels of genes associated with de novo lipogenesis (sterol regulatory element-binding protein 1c, acyl-CoA:diacylglycerol acyltransferase 2) were significantly enhanced in neoplasms. There was no significant difference in gene expression levels between carcinomas and adenomas, or between WOS-positive and WOS-negative neoplasms. Conclusion Gene expression profiles in neoplasms suggest a predominance of lipid storage (lipogenesis/LD formation) over consumption (β-oxidation/excretion/lipolysis). Lipid accumulation and WOS in gastric epithelial neoplasms may be caused by impaired mitochondrial oxidation, lipoprotein excretion, and LD degradation.

Background In this study, survival and cause of death were investigated in patients with Crohn’s disease (CD) at a tertiary referral center. Methods A database was created based on the medical records of 1108 CD patients who had a history of visiting our hospital to investigate background characteristics, cumulative survival rates from diagnosis, causes of death, and the standardized mortality ratio (SMR) for each cause of death. A follow-up questionnaire survey of patients followed up inadequately was also conducted. The cumulative survival rate from diagnosis was determined using the life table method and compared with that of a sex- and age-matched population model from the year 2000. Results The study included 1108 patients whose mean age at diagnosis was 25.6 ± 10.8 years. The mean duration of follow-up was 14.6 ± 9.4 years, and there were 52 deaths. The cumulative survival rate was significantly lower 25 years after the diagnosis of CD (91.7%) than in the standard population model (95.7%). SMRs for both all causes [3.5; 95% confidence interval (CI): 2.7–4.6] and CD-specific causes (36.7; 95% CI 26.1–51.6) were high. Among the CD-specific causes, SMRs were especially high for small intestine and colorectal cancers, gastrointestinal diseases including intestinal failure (IF), perioperative complications, and amyloidosis. Conclusion The SMRs for both all causes and CD-specific causes were high in CD patients. CD-specific causes including intestinal cancer, IF, perioperative complications, and amyloidosis showed especially high SMRs.

Background and Aims Gastric cancer is classified into differentiated and undifferentiated types according to the degree of glandular differentiation. Undifferentiated-type early gastric cancer (EGC) carries a higher risk of lymph-node metastasis than differentiated type, and therefore the indication criteria for endoscopic resection differ. This study aimed to clarify the ability of clinical predictors to distinguish between differentiated-type and undifferentiated-type EGCs. Methods This was a post hoc study of a multicenter prospective trial carried out in 5 Japanese hospitals, including 343 patients with cT1 EGC of ≥10 mm. According to the protocol, age, sex, and endoscopic findings of cancer (diameter, location, macroscopic type, and invasion depth) were evaluated, and the final diagnosis was confirmed from resected specimens. We evaluated the associations between these clinical factors and the histologic type of cancer and calculated the ability of the factors to diagnose differentiated-type EGC. The diagnostic ability of forceps biopsy was also calculated as a reference. Results Multivariate analysis identified older age (≥72 years), male sex, larger tumor size (>30 mm), elevated type, and shallower invasion depth (cT1a) as independent significant predictors for differentiated-type EGC, with elevated type showing the highest positive likelihood ratio. The sensitivity, specificity, accuracy, and positive and negative likelihood ratios of elevated type for differentiated-type EGC were 24%, 99%, 38%, 15.7, and 0.77, respectively, compared with 96%, 86%, 95%, 7.0, and 0.04 for forceps biopsy. Conclusions Endoscopic elevated type is a significant predictor for differentiated-type EGC and may exclude undifferentiated-type EGC without the need for forceps biopsy.

Background and aims Intestinal metaplasia (IM) of the stomach is associated with an increased risk of differentiated gastric cancer. While it is important to diagnose IM endoscopically, it can be difficult to observe by white-light endoscopy. In magnifying endoscopy with narrow-band imaging (M-NBI) of the stomach, a light-blue crest (LBC) is widely known to be a useful marker in the endoscopic diagnosis of IM. However, IM that exhibits only white opaque substance (WOS) without an LBC can also occur. The aim of this study was to elucidate whether the presence of WOS on M-NBI of the stomach could serve as a marker of IM in the same way that an LBC does. Methods The subjects were 40 consecutive patients who underwent M-NBI between July and December 2014. The primary endpoint in this study was to evaluate the diagnostic performance of M-NBI for histologically observed IM in WOS- and LBC-positive mucosa. Results The sensitivity and specificity of WOS for histologically diagnosed IM were 50.0 % (95 % confidence interval [CI] 40.0 % – 50.0 %) and 100.0 % (95 %CI 85.0 % – 100.0 %), respectively. Meanwhile, the sensitivity and specificity of LBC were 62.5 % (95 %CI 51.1 % – 65.9 %) and 93.8 % (95 %CI 76.7 % – 98.9 %), respectively. The sensitivity and specificity of WOS and/or LBC (WOS positive and LBC positive, WOS positive and LBC negative, or WOS negative and LBC positive) for histologically diagnosed IM were 87.5 % (95 %CI 76.9 % – 90.9 %) and 93.8 % (95 %CI 77.9 % – 98.9 %), respectively. Conclusions LBC and WOS are both useful markers for endoscopic diagnosis of IM. Combining both markers improves the sensitivity.Clinical trial number: UMINCTR000014453.

Background and Aim The prevalence of ulcerative colitis (UC) is increasing steadily in Japan. In Western countries, a bimodal distribution, with UC onset peaks in youth and middle age, is observed, and smoking cessation is reported as a risk factor for UC. However, there are few reports on a bimodal distribution of onset age among Japanese patients. Therefore, the distribution of onset age and factors related to late onset (i.e. onset at 50 years old or later) were investigated in UC patients in Japan. Methods A questionnaire survey of UC patients was conducted to investigate the distribution of the age of onset and factors that may be related to UC onset in a Japanese university hospital. Results Among 465 UC patients, 343 patients responded. In the distribution of onset age, a large peak was seen in patients aged 10–20s, and small peaks were seen at age 40–44 years and then in 50–60s. In addition, the onset age was older in the UC patients diagnosed in 2001 or later than in those diagnosed in 2000 or earlier. Late onset was more common among the UC patients diagnosed in 2001 or later (vs 2000 or earlier: interaction odds ratio = 4.98, 95% CI: 2.21–11.25, P

Background and Aim The aim of the present study was to endoscopically evaluate ileal mucosal healing during maintenance therapy with infliximab in order to investigate the clinical significance of endoscopic examination of ileal lesions in Crohn's disease patients. Methods This study retrospectively analyzed 54 patients who mainly had active ulcers of the ileum on endoscopy at baseline who were responsive to infliximab induction and who received infliximab maintenance therapy. Mucosal healing was defined as no ulcer or only ulcer scar. At the time of follow-up endoscopy after starting infliximab, endoscopic score, mucosal healing, and clinical remission were evaluated. On long-term follow up, correlations between mucosal healing and long-term clinical remission, and between mucosal healing and the need for major abdominal surgery, were also evaluated. Results Ileal mucosal healing and complete mucosal healing were significantly correlated with clinical remission (P = 0.046, P = 0.0001, respectively). The rate of long-term clinical remission was significantly higher in patients with complete mucosal healing (P = 0.025). The rate of major abdominal surgery for strictures was significantly lower in patients with complete mucosal healing (P = 0.044). Conclusions Complete mucosal healing after 1–2 years was a predictive factor for long-term clinical remission up to 4 years after starting infliximab. A lack of complete mucosal healing was a predictive factor for major abdominal surgery for strictures. The present study suggests that endoscopic evaluation of ileal lesions is useful for long-term prognosis of Crohn's disease patients.

Chromoendoscopy (CE) is relatively ineffective at identifying the cancer-specific morphological characteristics of minute gastric cancers less than or equal to 5 mm in diameter, and on its own is insufficient to make an accurate diagnosis. The aim of this study is to assess the diagnostic performance of magnifying endoscopy with narrow band imaging (M-NBI) for minute gastric cancers. The minute cancer group comprised consecutive endoscopic submucosal dissection-resected minute gastric cancers histologically measured as no larger than 5 mm in diameter. The non-cancer group comprised consecutive non-cancer lesions no larger than 5 mm in diameter. The two groups were subject to retrospective analysis to evaluate the diagnostic ability (sensitivity, specificity, and diagnostic accuracy) and reproducibility of CE and M-NBI. The results for CE versus M-NBI were as follows: sensitivity 43.7 % (95 % CI, 26.5–61.0 %) versus 78.0 % (95 % CI, 64.0–92.0 %); specificity 81.6 % (95 % CI, 72.6–90.6 %) versus 92.9 % (95 % CI, 87.0–98.9 %); and diagnostic accuracy 69.9 % (95 % CI, 61.0–78.6 %) versus 88.3 % (95 % CI, 82.0–94.5 %). The sensitivity and diagnostic accuracy were, therefore, significantly higher for M-NBI than for CE. The inter-observer variability was κ = 0.08 for CE and κ = 0.56 for M-NBI, while the intra-observer variability was κ = 0.38 and κ = 0.65, respectively. M-NBI has greater sensitivity and reproducibility than CE for the diagnosis of minute gastric cancers.

Crystal-storing histiocytosis (CSH) localized to the stomach is very rare, with only two cases reported to date. The present patient was a 55-year-old woman with no noteworthy symptoms. An area of discoloration was seen in the greater curvature of the gastric body on upper endoscopy by a local physician, and CSH was strongly suspected on biopsy examination. On upper endoscopy performed at our hospital, a flat, whitish, finely granular membrane with a diameter of 10 mm was seen in the greater curvature of the gastric body on white light observation. On magnifying endoscopy of the focal site, white granular material could be seen in the subepithelium, and the surface layer microvascular architecture image seen below the mucosal subepithelium was similar to the background, suggesting localization of the white material in a deep mucosal layer. On endoscopic ultrasound, this was depicted as multiple hyperechoic spots within the second layer corresponding to the involved area. Endoscopic submucosal dissection (ESD) was performed for a definitive diagnosis. Histopathological assessment of resected specimens revealed infiltration of abundant histiocytes including acidophilic crystalline structured material and positive plasma cells on anti-κ chain immunostaining, and CSH was diagnosed. Since this patient could have had a concomitant background autoimmune or hematologic disease, a systemic search was done. During this search, comorbid Sjögren's syndrome was discovered. This case of asymptomatic Sjögren's syndrome discovered during investigation of very rare gastric CHS is reported.

Because endoscopic submucosal dissection (ESD) of gastric cancer can only be curative if the cancer is detected at an early stage and a precise preoperative diagnosis is made, we reviewed the detection and characterization of early gastric cancer (EGC) using both conventional endoscopy with white-light imaging (C-WLI) and image-enhanced endoscopy (chromoendoscopy [CE] and magnifying narrow-band imaging [M-NBI]). Systematic screening of the stomach by C-WLI after ideal preparation of the patient is important for detecting a mucosal lesion, which can then be characterized using CE. However, a limitation of C-WLI with CE is the diagnosis of flat or small gastric cancers. To overcome this, M-NBI together with a comprehensive diagnostic system, termed the 'vessel plus surface classification' system, was developed and has proven very useful. Preoperative assessment for ESD involves determining: (i) histological type; (ii) size; (iii) depth of invasion; (iv) presence or absence of associated ulceration; and (v) horizontal extent of the cancer. A limitation of endoscopic diagnosis using M-NBI is the histologically undifferentiated type of carcinoma, in which case the biopsy specimen is used to make a histopathological diagnosis.

Background/Aims: In Japan, aphthous-type Crohn's disease (type A CD) is thought to represent an early phase of Crohn's disease (CD), and diagnosis of type A CD is possible in the diagnostic criteria for CD in Japan. However, the details of type A CD are not well understood. Methods: Subjects comprised 649 CD patients diagnosed between 1985 and 2011. The incidence of type A CD over time was clarified in two periods (1985-2004 and 2005-2011). The course of type A CD was also investigated, and cases that did and did not progress to typical CD were compared. Results: No significant difference was seen in the incidence of type A CD between the two periods (5.2 vs. 8.5%, p = 0.125). Type A CD patients followed at our hospital progressed to typical CD at a rate of 59.3%. In comparing progressive and nonprogressive cases, the frequency of large, densely distributed aphthous lesions in the small intestine was higher among progressive cases (p = 0.018). Conclusion: Type A CD is an early phase of CD, and CD diagnostic criteria including early cases are valid in Japan.

Background and study aims: We previously reported our discovery of a white opaque substance (WOS) that is opaque to endoscopic light inside the epithelium while using magnifying endoscopy (ME) to examine gastric epithelial neoplasia. Histopathologic analysis revealed that the WOS comprises minute lipid droplets (LDs) accumulated within the neoplastic epithelium. In addition, the WOS was found in colorectal epithelial neoplasia, although it was unclear whether this WOS corresponded to an accumulation of LDs, as in the stomach. Therefore, the aim of the current study was to elucidate whether the WOS observed in colorectal epithelial tumors comprises LDs. Patients and methods: A consecutive series of 40 WOS-positive and 40 WOS-negative colorectal epithelial tumors was analyzed. One biopsy specimen was taken from each neoplasm. Cryostat sections were stained with oil red O for LD, and sections after formalin-fixation for LD were immunostained with anti-adipophilin antibody. Results: The prevalence of LDs stained with oil red O in WOS-positive vs. WOS-negative lesions was 47.5 % (19/40) vs. 5 % (2/40), respectively (P

Background: Endoscopic submucosal dissection (ESD) is an outstanding endoscopic technique in which a colonic lesion can be resected en-bloc. However, the procedure requires a high level of skill and the procedure has yet to be standardized. At the present time, colorectal ESD is only permitted in Japanese institutions that have been certified for advanced medical treatments. Methods: We examined 200 cases of colorectal ESD that were performed in our hospital. Results: Over time, it was found that there was a continuous improvement in the treatment outcomes along with advances in both the procedures and the peripheral equipment utilized. Conclusion: Current results suggest that the colorectal ESD procedure is relatively stable. To ensure colorectal ESD continues to be safe, indications for its use need to be more fully investigated and medical personnel must be trained to carefully perform the procedure.

Aim: We assessed the long-term outcome of infliximab (IFX) therapy in patients with Crohn's disease (CD) and investigated the efficacy of concomitant endoscopic balloon dilation (EBD) for intestinal stricture during treatment. Methods: The effectiveness of maintenance therapy with IFX was retrospectively evaluated in 185 patients with CD in a single center (median observation period 24 months). IFX effectiveness with and without immunomodulators (IMM) and enteral nutrition (EN), as well as cumulative surgery-free rates, were compared. The efficacy of concomitant EBD in patients with obstructive symptoms and high-level stricture was evaluated. Results: In 185 patients receiving the maintenance therapy, the long-term efficacy rate was 84.9% at 24 months and 79.0% at 48 months. The cumulative surgery-free rate was significantly higher in the maintenance group (P

1 Endoscopy, 2 Pathology and 3 Background and Aims: Magnifying endoscopy (ME) with narrow-band imaging (NBI) revealed a white opaque substance (WOS) within the superficial part of the gastric neoplasia; however, its nature has remained obscure.A WOS noted within the duodenum was reported to comprise lipid droplets (LD) absorbed by the duodenal epithelium. We attempted to ascertain whether the WOS within gastric neoplasia could also comprise LD and whether the presence of this WOS could be correlated with a specific phenotype. Methods: Forty-three patients with early gastric epithelial neoplasia underwent ME with NBI.The presence or absence of WOS in the neoplasias was recorded based on the findings of ME with NBI. One biopsy specimen was taken from each of the neoplasias. Cryostat sections underwent oil red O staining for LD. Serial sections were immunostained using the first antibody of CD10, MUC2, CDX2, human gastric mucin, MUC5AC and MUC6. The tissue phenotype was classified as intestinal (I),gastric (G) and gastrointestinal (GI) type based on the results of immunostaining.In total,49 gastric neoplasias from 43 patients were investigated. Results: Prevalence of LD in WOS-positive versus WOS-negative lesions was 96.2% (25/26) and 4.3% (1/23), respectively (P < 0.001, Fisher's exact test).WOS was present in GI- and I-type lesions, but not in G-type lesions. Conclusions: WOS may be LD that have been accumulated in the superficial part of the gastric neoplasia of a certain intestinal phenotype.

Background: Although rare, duodenal lesions have been reported in association with ulcerative colitis (UC); however, there have been very few reports on small bowel lesions, and many aspects of their pathology and frequency remain unknown. This study determined whether small bowel lesions are present in UC by using wireless capsule endoscopy (WCE). Patients and Methods: WCE was performed on 20 patients with active UC and 10 who had undergone proctocolectomy. Results: Small bowel lesions (e.g. edema or ulcers) were observed in 11 of the 30 patients (36.6%): in eight (40%) of the 20 patients with active UC and in three (33.3%) of the 10 post-proctocolectomy patients. Ulcers that extended over a long segment or whole tertile of the small bowel were observed in five patients, and the disease type was extensive colitis in three of these and pouchitis in the other two. Age at onset was significantly lower in the 20 active UC patients that had small bowel lesions. Conclusion: WCE revealed the presence of ulcers that extended over a long segment or a whole tertile in the small bowel in active extensive colitis and pouchitis. In future, it will be necessary to assess the clinical significance of small bowel lesions in UC in detail.

Background Few studies have evaluated the degree of pain, the amount of retained gas, and the safety of carbon dioxide (CO 2 ) insufflation in patients undergoing double-balloon enteroscopy (DBE). Objective To clarify the usefulness and safety of CO 2 insufflation during DBE. Design Single-center, prospective, randomized, double-blind, controlled trial. Setting University hospital. Patients Forty eligible patients with small-bowel disease for whom DBE was indicated were randomized to a CO 2 insufflation (CO 2 ) group or an air insufflation (air) group by means of sealed envelopes. Intervention DBE with insufflation of CO 2 or air. Main Outcome Measurements Efficacy evaluation was based on the degree of pain as assessed by use of a visual analog scale (VAS) and the amount of residual gas retention within the small and large bowels on radiography. The safety of CO 2 insufflation was evaluated by arterial blood gas analysis. Results Significantly fewer patients in the CO 2 group had severe pain of ≥50 mm on the VAS during DBE than in the air group ( P = .02). Significantly less gas was retained in the small bowel just after and at 3 hours after DBE in the CO 2 group than in the air group ( P = .003, P = .01, respectively). There was significantly less residual gas retention in the large bowel at 3 hours after DBE in the CO 2 group than in the air group ( P = .02). There was no significant difference in pre-DBE and post-DBE partial pressure of oxygen in the blood (PaO 2 ) and partial pressure of carbon dioxide in the blood (PaCO 2 ) between groups. Limitations Small sample size. Conclusion CO 2 insufflation is a safe and useful procedure when performed during DBE.

Two patients with granulomatous lung lesions thought to be related to Crohn's disease (CD) are reported. Patient 1 was a 43-year-old man who was diagnosed with CD at age 11 years. He developed a fever in the 38 °C, and a chest X-ray and CT scan showed infiltrates with air bronchograms in the right upper lobe and left lingular segment. Transbronchial lung biopsy (TBLB) revealed granulomatous lesions. Patient 2 was a 76-year-old woman who was diagnosed with CD at age 44 years. Chest CT showed infiltrates and nodular shadows in both lung fields. Video-assisted thoracoscopic surgery (VATS) in June 2012 revealed granulomatous lesions. Tuberculosis, fungal infections, drug-induced lung disorder, and sarcoidosis were ruled out as a cause of the granulomatous lesions in both patients. The aetiology was thought to be CD.

Aim: Recent reports have focused on the development of secondary amyloidosis (AMY) as a complication of Crohn's disease (CD). The present study was carried out to investigate the frequency of AMY secondary to CD, its clinical and endoscopic features, and the importance of duodenal biopsy in detecting this disease. Methods: This study involved 408 patients diagnosed with CD who were endoscopically and histologically examined at our hospital. At follow up, we analyzed the incidence of AMY complications, the clinical features of AMY and the methods to diagnose AMY. Results: The incidence of AMY was 2.5% (10/408). The disease type at the time of CD diagnosis was small and large bowel type (SL) in eight patients, small bowel type in one and large bowel type in one. The incidence of AMY was significantly higher in patients with SL than in patients with other disease types. The length of time from onset of CD to diagnosis of AMY was 14.1 ± 8.0 years. The cumulative incidence of AMY was 1.0% at 10 years and 5.7% at 20 years after onset. In terms of the method used to diagnose AMY, the positive rate of AMY diagnosis was 100% with endoscopic duodenal biopsy. Conclusion: The incidence of AMY as a complication of CD was low (2.5%). However, because this complication adversely affects patients' prognoses, it is important to check for the presence of AMY, particularly in the duodenum, in patients for whom more than 10 years have elapsed since the development of CD.

Background and Aim: Ulcerative colitis (UC) is not only characterized by pathological lesions localized to colonic mucosa, but also to various complications involving other organs, including postoperative pouchitis. Among these complications, diffuse gastroduodenitis with lesions resembling colonic lesions has been reported, albeit rarely. The aim of the present study was to attempt to characterize the lesions of the upper gastrointestinal tract occurring as a complication of UC, and to assess the frequency and clinical course of these lesions. Methods: A total of 322 UC patients who had undergone upper gastrointestinal endoscopy were retrospectively analyzed. We assessed the frequency of endoscopic findings, including diffuse gastroduodenal lesions resembling colonic lesions. Ulcerative gastroduodenal lesion (UGDL) associated with UC was diagnosed if lesions satisfied the following criteria: (i) improvement of the lesions with treatment of UC; and/or (ii) resemblance to UC in pathological findings. Results: UGDL satisfying the aforementioned criteria was found in 15 (4.7%) of 322 patients. All the 15 patients had UGDL accompanied by pancolitis or after proctocolectomy. Frequency in 146 patients with pancolitis was 6.2% (nine patients) and that in 81 patients who had undergone proctocolectomy was 7.4% (six patients). Four patients with diffuse ulcerative upper-gastrointestinal mucosal inflammation (DUMI) had pouchitis. In all patients except one, the lesions resolved easily with medical treatment. Conclusions: In more than half of the post-proctocolectomy patients, UGDL was related to the occurrence of pouchitis. The existence of characteristic UGDL must be taken into account in the diagnosis and treatment of UC, and UGDL is possibly related to the occurrence of pouchitis.

Background/Aims: Decreased trough levels of infliximab (TLI) and antibodies to infliximab (ATI) are associated with loss of response (LOR) in Crohn’s disease. Two prospective studies were conducted to determine whether TLI or ATI better correlates with LOR (Study 1), and whether TLI could become a predictor of mucosal healing (MH) (Study 2). Methods: Study 1 was conducted in 108 patients, including those with LOR and remission to compare ATI and TLI in discriminating the 2 conditions based on receiver operating characteristic (ROC) curve analyses. Study 2 involved 35 patients who were evaluated endoscopi cally. Results: In Study 1, there were no differences between the 2 assays in ROC curve analyses; the TLI cutoff value for LOR was 2.6 μg/mL (sensitivity, 70.9%; specificity, 79.2%), and the ATI cutoff value was 4.9 μg/mL (sensitivity, 65.5%; specificity, 67.9%). The AUROC (area under the ROC curve) of TLI was greater than that of ATI. AUROC was useful for discriminating be tween the 2 conditions. In Study 2, the TLI was significantly higher in the colonic MH group than in the non-MH group (2.7 μg/mL vs. 0.5 μg/mL, P=0.032). Conclusions: TLI is better than ATI for clinically diagnosing LOR, and a correlation was observed between TLI and colonic MH. (Intest Res 2018;16:223-232)

Aim: The present study was aimed at evaluating the efficacy of azathioprine (AZA) in patients with active and relapsing Crohn's disease (CD) and the usefulness of endoscopy in this evaluation. Methods: The 53 patients with active CD treated with AZA at our hospital were subjected to the following retrospective analysis: (i) evaluation of the clinical efficacy of AZA through comparison of the Crohn's disease activity index (CDAI); (ii) analysis of the relationship of the clinical efficacy to the difference in the mean corpuscular volume (MCV); (iii) evaluation of mucosal healing through analysis of the scores of the endoscopic findings in 16 patients; and (iv) analysis of the relapse rate. Results: (i) Among the 53 patients, treatment was rated as having induced complete remission in 22.6%, as being effective in 41.5%, and as being ineffective in 13.3% of patients. The treatment was discontinued in 22.6% of patients. (ii) The post-treatment MCV was significantly increased after treatment. (iii) When the ulcer score estimated after treatment was compared with that before the start of treatment, a significant improvement of the score was noted. (iv) When the non-relapse rate after AZA therapy was calculated in the 41 patients followed up for 12 months, it was 84.8%. Conclusion: AZA was shown to cause endoscopic mucosal healing as well as clinical efficacy. In the present study, it was inferred that the efficacy of AZA therapy in CD patients is manifested clinically first and that mucosal healing is an effect that occurs later.

Background The microvascular pattern (MVP) as visualized by magnification endoscopy (ME) is a reliable marker for differentiating between benign and malignant gastric flat lesions. However, in cases of gastric neoplasia of 0-IIa type, it is sometimes impossible to visualize the MVP because a white opaque substance (WOS) obscures the subepithelial MVP. Objective To investigate whether the morphology of the WOS could be a useful optical sign for discriminating between adenoma and carcinoma. Setting Single tertiary referral center. Materials Forty-six gastric neoplasias of only 0-IIa type (18 adenomas and 28 early carcinomas) were evaluated. Intervention The prevalence and the morphology of the WOS as visualized by ME with narrow-band imaging (NBI) according to histologic type (adenoma vs carcinoma). Main Outcome Measurements The WOS is more frequently present in adenomas than in carcinomas. With regard to the morphology of the WOS, 100% of the examples of WOS within adenomas demonstrated a regular distribution; in contrast, 83% of the examples of WOS within carcinomas showed an irregular distribution. Results In cases in which a neoplasia of 0-IIa type showed either WOS with a regular distribution or a regular MVP, the sensitivity and specificity for discriminating adenoma from carcinoma were 94% and 96%, respectively. Limitations The number of cases was limited. The WOS has not yet been characterized by chemical analysis. Conclusion In cases in which the WOS is observed, rather than assessing the MVP, morphologic analysis of the WOS could be an alternative new optical sign for discriminating adenoma from carcinoma when using ME with NBI.

Background & Aims: During gastroscopy we frequently encounter flat reddened lesions in the stomach. Making a correct diagnosis of flat small early gastric cancer is dependent not on endoscopic diagnosis, but on histopathologic diagnosis of biopsy specimens alone. We investigated the diagnostic accuracy of magnified endoscopic findings for differentiating between reddened mucosa caused by gastritis and flat reddened gastric cancer, prospectively and blindly. Methods: A total of 603 consecutive patients were examined by upper-gastrointestinal zoom endoscopy and the prevalence of each of the following magnified endoscopic findings, which already had been reported as characteristic for differentiated carcinoma, was recorded: (1) presence of a demarcation line between the reddened lesion and the surrounding mucosa, (2) disappearance of the regular subepithelial capillary network pattern, and (3) presence of an irregular microvascular pattern within the flat reddened lesion. Patients with known gastric carcinomas were excluded from this study. Results: A total of 158 flat reddened lesions from 158 patients were detected. Pathologically, 144 flat reddened lesions showed only gastritis, whereas 14 lesions were newly diagnosed as carcinoma. Regarding diagnostic accuracy for carcinoma, the negative predictive values of the presence of a demarcation line and disappearance of the regular subepithelial capillary network pattern were 100% and 100%, respectively, and the diagnostic accuracy of the irregular microvascular pattern was 98.7%. Conclusions: The novel zoom endoscopic findings based on microvascular architecture are very useful for making a differential diagnosis between flat early gastric carcinoma and gastritis.

White opaque substance (WOS) is a novel endoscopic finding in gastric neoplasms, indicating the intracellular accumulation of lipid droplets (LDs). However, gastric lipid metabolism has not been extensively investigated, even in normal mucosa. We investigated the expression profiles of lipid-metabolism-associated genes in gastric neoplasms.Thirty-four patients with early gastric cancer or adenoma were enrolled in this study. Paired biopsy samples from tumor and adjacent non-tumor areas were obtained and analyzed by real-time polymerase chain reaction. Endoscopically resected specimens were evaluated histopathologically.Genes associated with β-oxidation (peroxisome proliferator-activated receptor α, carnitine palmitoyltransferase 1A, and hydroxyacyl-CoA dehydrogenase), lipoprotein excretion (apolipoprotein B, microsomal triglyceride transfer protein, and acyl-CoA:cholesterol acyltransferase 2), fatty acid transport (fatty acid-binding protein), construction of triglycerides in the endoplasmic reticulum (acyl-CoA:diacylglycerol acyltransferase 1), and LD degradation/lipolysis (comparative gene identification-58, adipose triglyceride lipase) were significantly downregulated in neoplasms compared with non-tumor areas. Pyruvate dehydrogenase lipoamide kinase isozyme 4 (negative regulator of glycolysis) and adipophilin (LD surface component) were also repressed. Conversely, expression levels of genes associated with de novo lipogenesis (sterol regulatory element-binding protein 1c, acyl-CoA:diacylglycerol acyltransferase 2) were significantly enhanced in neoplasms. There was no significant difference in gene expression levels between carcinomas and adenomas, or between WOS-positive and WOS-negative neoplasms.Gene expression profiles in neoplasms suggest a predominance of lipid storage (lipogenesis/LD formation) over consumption (β-oxidation/excretion/lipolysis). Lipid accumulation and WOS in gastric epithelial neoplasms may be caused by impaired mitochondrial oxidation, lipoprotein excretion, and LD degradation.

Background and study aims: The authors have successfully demonstrated that the white opaque substance (WOS) identified in gastric epithelial neoplasms is an accumulation of minute lipid droplets on the epithelial neoplasm. It is not known whether the lipid droplets originate from externally ingested lipids (typically foods). The purpose of this study was to investigate whether the oral ingestion of foods containing emulsified fats increases the density of the WOS in epithelial neoplasms. Patients and methods: We examined 92 gastric epithelial neoplastic lesions in 89 patients. The patients were given emulsified fatty foods before the procedure, and magnifying endoscopy with narrow-band imaging (M-NBI) was used to image the lesions. An increase in WOS density after the ingestion of emulsified fatty foods was defined as a positive fat-loading test result. The patients were divided into the following groups: control group, no emulsified fat administered; group 1, fatty food administered 16 hours prior; group 3, fatty food administered both 16 and 4 hours prior. The proportion of positive fat-loading test results was determined in all groups. Results: The rates of positive fat-loading test results were as follows: control group, 9 %; group 1, 26 %; group 2, 52 %; group 3, 78 %. The increase in the rates of positive fat-loading test results in groups 2 and 3 relative to the rate in the control group was statistically significant (chi-squared test). Conclusions: This study demonstrated for the first time that the ingestion of external lipids causes lipid droplets to aggregate in situ on the gastric epithelial neoplasm. These results can be used to develop a novel functional endoscopy technique that harnesses the lipid absorption capacity of neoplasms.

Background: Intestinal mucosal lesions in Crohn's disease were endoscopically evaluated before and after giving infliximab, and the usefulness of this treatment was investigated. Patients and methods: The present study included 12 patients with active Crohn's disease who could undergo colonoscopy before and after giving infliximab. (i) The treatment assessment consisted of evaluations of short-term and long-term therapeutic effects. The clinical evaluation was conducted using the Crohn's disease activity index (CDAI). The results of the clinical evaluation were compared with those of the colonoscopic evaluation. (ii) The endoscopic evaluation findings were divided into polyposis, ulcer and stenosis, and the area ranging from the rectum to the terminal ileum. The scores for the findings at seven sites were totaled. In the short-term therapeutic effect, characteristics of ulcer morphology and background factors were investigated endoscopically. Results: (i) The efficacy rate was 92% clinically and 67% endoscopically in the evaluation of short-term therapeutic effects. The efficacy rate was 86% clinically and 86% endoscopically in the evaluation of long-term therapeutic effects. (ii) On the endoscopic evaluation, the ulcer score was significantly (P = 0.03) improved after giving infliximab, while there was no remarkable change in the polyposis score and the stenosis score tended to worsen. On the evaluation of therapeutic effects based on ulcer morphology, infliximab was endoscopically effective in patients with longitudinal ulcers. On the evaluation of therapeutic effects based on background factors, the treatment was effective in patients given a combination of infliximab and immunosuppressants. Conclusion: The ulcerative lesions were found to be markedly improved, but the intestinal stenosis tended to worsen, after giving infliximab. It is necessary that the severity of intestinal stenosis be adequately understood before giving infliximab. Giving immunosuppressants should be used for combined treatment.

We have developed and established a zoom endoscopy technique based on visualization of the mucosal microvascular architecture in units as small as the capillary in the normal stomach and early gastric cancer. With regard to the microvascular architecture of the normal stomach, the findings differed according to the section of the stomach. The gastric body showed a honeycomb-like subepithelial capillary network pattern with collecting venule, whereas the gastric antrum showed a coil-shaped subepithelial capillary network pattern. Regarding early gastric cancer, the following findings seemed to be specific for differentiated carcinoma: (1) a demarcation line between the cancerous and the noncancerous mucosa, (2) the disappearance of the regular subepithelial capillary network pattern, and (3) the presence of an irregular microvascular pattern. These findings, which were visualized by magnified observation, could be useful in clinical practice when we attempt to make a correct endoscopic diagnosis of flat reddened lesions (gastritis vs cancer) and when we attempt to determine the precise horizontal margin of early gastric cancer. This could help us to perform successful endoscopic resection based on endoscopic findings alone. In conclusion, our zoom endoscopy for visualizing the microvascular architecture in gastric mucosa could be a new system for diagnosing early gastric cancer.

Intestinal complications of stenosis or fistula may occur during the course of Crohn's disease (CD), and surgery is performed in a fair number of patients. The risk factors for initial surgery in a Japanese hospital-based cohort of CD patients were evaluated.This study was a single-center, retrospective, cohort study. The subjects were 520 patients who underwent inpatient and outpatient treatment at our hospital, had a definitive diagnosis of CD, and no previous surgery. Three parameters were investigated: (i) cumulative incidence of stenosis and fistula; (ii) cumulative rate of initial surgery for each disease type; and (iii) risk factors at diagnosis for initial surgery.(i) Stenosis and fistula increased with time, with stenosis or fistula appearing in about half of the patients after 5 years. (ii) The cumulative rate of initial surgery was about 50% after 10 years. (iii) The patient factors at diagnosis of current smoker, upper gastrointestinal disease, stricturing, penetrating, moderate to severe stenosis of the jejunum, moderate to severe stenosis of the ileum, and moderate to severe stenosis of the terminal ileum were risk factors for initial surgery.Stenosis or fistula appeared in about half of the patients after 5 years from diagnosis. When upper gastrointestinal disease or complicated small intestinal lesions are seen at the time of diagnosis, the cumulative rate of initial surgery is significantly higher.

The prevalence of ulcerative colitis (UC) is increasing steadily in Japan. In Western countries, a bimodal distribution, with UC onset peaks in youth and middle age, is observed, and smoking cessation is reported as a risk factor for UC. However, there are few reports on a bimodal distribution of onset age among Japanese patients. Therefore, the distribution of onset age and factors related to late onset (i.e. onset at 50 years old or later) were investigated in UC patients in Japan.A questionnaire survey of UC patients was conducted to investigate the distribution of the age of onset and factors that may be related to UC onset in a Japanese university hospital.Among 465 UC patients, 343 patients responded. In the distribution of onset age, a large peak was seen in patients aged 10-20s, and small peaks were seen at age 40-44 years and then in 50-60s. In addition, the onset age was older in the UC patients diagnosed in 2001 or later than in those diagnosed in 2000 or earlier. Late onset was more common among the UC patients diagnosed in 2001 or later (vs 2000 or earlier: interaction odds ratio = 4.98, 95% CI: 2.21-11.25, P0.01) and among former smokers (vs never-smokers: interaction odds ratio = 2.93, 95% CI: 1.40-6.14, P0.01) on multivariate analysis.Similar to UC patients in Western countries, a bimodal distribution of onset age was also observed in Japanese UC patients, and smoking cessation may partly contribute to the increase in late-onset UC patients in recent years in Japan.

The portal venous (p.v.) administration of foreign cells induces donor-specific tolerance. Recently, we have demonstrated that the p.v. administration of donor cells elicits donor-specific tolerance across major histocompatibility complex barriers. In the present study, utilizing the intrahepatic tolerance-inducing system, we have established a new method for organ transplantation using both busulfan ([Bu] to provide a sufficient “space” for the donor hematopoietic cells to expand in the recipient) and neuraminidase ([Neu] to enhance the trapping of i.v.-injected cells in the liver). Radiolabeled bone marrow cells (BMCs) were found to exclusively accumulate in the livers of the recipients as a result of the Neu treatment. Furthermore, hematopoietic progenitors (forming hematopoietic foci) in the accumulated BMCs were retained in the recipient livers for at least 18 days. C57BL/6 (B6) mice that had been transplanted with skins of BALB/c mice immediately after the injection of BALB/c BMCs showed a 90% skin graft survival rate over 400 days as a result of using the combination of injecting 50 mg/kg Bu into the B6 mice and treatment of the BALB/c BMCs with 0.25 U/ml Neu (50 Bu + 0.25 Neu). However, the survival rate significantly decreased when either the Bu or Neu treatment was omitted. In tolerant recipients, microchimerism was observed in the various hematolymphoid organs. T cells collected from the tolerant recipients suppressed proliferative responses to the donor-alloantigens but enhanced the production of Th2 and Th3 cytokines. These findings suggest that the enhanced retention of donor BMCs in the recipient livers as a result of the Bu and Neu treatments efficiently induces tolerance induction. Therefore, this “single-day protocol” would be of great advantage for human organ transplantation.

Background. It has been shown that allogeneic bone marrow transplantation (BMT) after lethal irradiation elicits donor-specific tolerance for organ or tissue transplantation across major histocompatibility complex (MHC) barriers. Recently, we have demonstrated that the portal venous (p.v.) administration of donor bone marrow cells (BMCs) elicits donor-specific tolerance across MHC barriers by only two administrations of an immunosuppressant (CsA or FK-506). In our study, using the central and intrahepatic tolerance-inducing system, we have established a new method for thyroid transplantation with BMT that would be more applicable to humans. Methods. In addition to sublethal (6-5 Gy) irradiation, recipient B6 (H-2 b ) mice received injections i.p. with the myeloablative drug busulfan (BU) on day -2 to provide a sufficient space for the donor hemato-poietic cells to expand in the recipients. To induce the intrahepatic tolerance, donor BALB/c (H-2 d ) BMCs were treated with neuraminidase (Neu), which enhances the trapping of i.v. injected BMCs in the liver. After the injection of Neu-treated BMCs, the thyroid organs from the BALB/c mice were engrafted under the renal capsules. Results. A 90% graft survival rate was obtained over 100 days by a combination of BU administration, 6 Gy irradiation, and i.v. injection of Neu-treated BMCs [BU+6 Gy+(Neu) i.v.], and a 70% graft survival rate was obtained by [BU+5 Gy+(Neu) i.v.]. However, the graft survival rate significantly decreased when either the BU or Neu treatment was omitted. T cells collected from the tolerant recipients suppressed the proliferative responses to donor alloantigens. Conclusions. Using both BU and Neu treatments, we have succeeded in inducing long-term tolerance and preventing the rejection of thyroid allografts by the single-day protocol.

The injection of allogeneic cells via the portal vein (p.v.) is known to reduce responses to donor-alloantigens. In the present study, we have obtained persistent tolerance across Mls and multiple minor histocompatibility complexes by p.v. preimmunization followed by the administration of cyclophosphamide (CY). A hundred percent survival of (BALB/c x DBA/2)F1 (CDF1) skin grafts for more than 200 days was observed when BALB/c mice were preimmunized with spleen cells of CDF1 (3 x 10(7)) via the p.v. and administered 300 mg/Kg CY 2 days after the p.v. injection. Comparable survival of the skin graft was observed when bone marrow cells instead of spleen cells were p.v. preimmunized. However, the survival rate was significantly decreased when LPS-stimulated blastic cells were p.v. preimmunized. Microchimerism has been observed in the liver, thymus, bone marrow and peripheral blood of recipients. V beta 6+ cells decreased in CD4+ cells of recipients of the p.v. preimmunization plus CY treatment. However, there was no difference in the decrease in V beta 6+ cells between recipients accepting the CDF1 skin grafts and recipients that had rejected the skin grafts. Furthermore, no intrathymic depletion of the V beta 6+ cells was observed. From these results, it is suggested that, rather than clonal deletion, other mechanisms such as clonal anergy or suppression may be involved in the induction of persistent tolerance after the p.v. preimmunization plus CY treatment.